Deep Learning Model for Predicting Intradialytic Hypotension Without Privacy Infringement: A Retrospective Two-Center Study.

Objective: Previously developed Intradialytic hypotension (IDH) prediction models utilize clinical variables with potential privacy protection issues. We developed an IDH prediction model using minimal variables, without the risk of privacy infringement. Methods: Unidentifiable data from 63,640 hemodialysis sessions (26,746 of 79 patients for internal validation, 36,894 of 255 patients for external validation) from two Korean hospital hemodialysis databases were finally analyzed, using three IDH definitions: (1) systolic blood pressure (SBP) nadir <90 mmHg (Nadir90); (2) SBP decrease ≥20 mmHg from baseline (Fall20); and (3) SBP decrease ≥20 mmHg and/or mean arterial pressure decrease ≥10 mmHg (Fall20/MAP10). The developed models use 30 min information to predict an IDH event in the following 10 min window. Area under the receiver operating characteristic curves (AUROCs) and precision-recall curves were used to compare machine learning and deep learning models by logistic regression, XGBoost, and convolutional neural networks. Results: Among 344,714 segments, 9,154 (2.7%), 134,988 (39.2%), and 149,674 (43.4%) IDH events occurred according to three different IDH definitions (Nadir90, Fall20, and Fall20/MAP10, respectively). Compared with models including logistic regression, random forest, and XGBoost, the deep learning model achieved the best performance in predicting IDH (AUROCs: Nadir90, 0.905; Fall20, 0.864; Fall20/MAP10, 0.863) only using measurements from hemodialysis machine during dialysis session. Conclusions: The deep learning model performed well only using monitoring measurement of hemodialysis machine in predicting IDH without any personal information that could risk privacy infringement.

Nationwide Implementation of Nonpharmaceutical Interventions During the Coronavirus Disease 2019 Pandemic Is Associated With Decreased Incidence of Pneumocystis jirovecii Pneumonia in Kidney Transplant Recipients.

This study aimed to investigate the impact of nationwide nonpharmaceutical interventions against coronavirus disease 2019 (COVID-19) on the incidence of Pneumocystis jirovecii pneumonia (PCP) in kidney transplant recipients. The monthly incidence of PCP during the COVID-19 period decreased significantly compared to that of the pre-COVID-19 period in kidney transplant recipients.

Exercise reduces the risk of chronic kidney disease in individuals with nonalcoholic fatty liver disease: A nationwide cohort study.

AIMS: Recent studies of individuals with nonalcoholic fatty liver disease (NAFLD) have indicated benefits of exercise in improving outcomes. We investigated whether exercise reduces the risk of chronic kidney disease (CKD) in individuals with NAFLD. METHODS: A total of 7275 participants from the Korea National Health and Nutrition Examination Survey (KNHANES) cohort, and 40,418 participants with NAFLD from the National Health Insurance Service (NHIS) cohort were included for the cross-sectional and longitudinal analyses, respectively. For the cross-sectional analysis, the primary outcome was prevalent CKD, defined as an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73m2. For the longitudinal analysis, the primary outcome was incident CKD, defined as the occurrence of eGFR <60 mL/min/1.73m2 or proteinuria (≥ trace) on two consecutive measurements during follow-up. RESULTS: In the KNHANES cohort, prevalent CKD was observed in 229 (6.1%), 48 (2.6%), and 36 (2.1%) participants in the 0, 1-2, and ≥ 3 exercise sessions/week groups, respectively. The likelihood of prevalent CKD was lowest in participants allocated to the ≥ 3 sessions/week group (adjusted OR 0.49; 95% CI, 0.33-0.71; P < 0.001). During a median follow-up of 5.0 years in the NHIS cohort, incident CKD occurred in 1,047 (9.7/1,000 person-years), 188 (7.3/1,000 person-years), and 478 (7.4/1,000 person-years) participants in the 0, 1-2, and ≥ 3 sessions/week groups, respectively. The risk of incident CKD was lowest in participants allocated to the ≥ 3 sessions/week group (adjusted HR 0.85; 95% CI, 0.76-0.95; P = 0.004). CONCLUSIONS: Exercise was significantly associated with a reduced risk of both prevalent and incident CKD in individuals with NAFLD.

The effects of wearing a face mask and of subsequent moisturizer use on the characteristics of sensitive skin.

BACKGROUND: COVID-19 is a serious respiratory disease, and wearing masks has become essential in daily life. Nevertheless, the number of people complaining of skin problems caused by wearing masks is increasing. Therefore, we investigated the characteristics of changes in sensitive skin caused by wearing a mask. MATERIALS AND METHODS: Twenty healthy Korean women with sensitive skin participated in this study. To determine any skin-related changes caused by mask-wearing, we evaluated redness, hydration, transepidermal water loss (TEWL), and moisture at 2.5 mm below the surface before and 4 h after wearing a Korea Filter 94 mask. In addition, we tested whether applying a moisturizer for 30 min after mask removal could reverse any mask-induced changes. RESULTS: Skin redness and TEWL were significantly increased at 4 h after wearing a mask (p < 0.05), otherwise skin hydration and the 2.5 mm moisture were significantly decreased (p < 0.05). After applying the moisturizer, skin redness and TEWL were significantly decreased compared to their values 4 h after wearing masks (p < 0.05), whereas skin hydration and the 2.5 mm moisture were significantly increased (p < 0.05). Moreover, after applying the moisturizer, skin redness and TEWL were significantly reduced compared to the pre-masking baseline (p < 0.05), whereas skin hydration was significantly increased (p < 0.05); the 2.5 mm moisture showed no significant change. CONCLUSION: We observed that wearing masks causes physiological changes in sensitive skin, whereas applying a moisturizer after removing the mask improved skin conditions.

Metabolic dysfunction-associated fatty liver disease and risk of incident chronic kidney disease: A nationwide cohort study.

AIMS: The recently proposed metabolic dysfunction-associated fatty liver disease (MAFLD) has been suggested to better reflect the metabolic components of fatty liver disease (FLD), compared to nonalcoholic fatty liver disease (NAFLD). This study investigated whether MAFLD identifies a higher proportion of individuals at risk of developing chronic kidney disease (CKD). METHODS: 268,946 participants aged 40-64 years, who underwent National Health Insurance Service health examinations between 2009 and 2015 were included. Participants were categorized by presence of FLD, according to MAFLD or NAFLD. In participants with FLD, participants were categorized into three groups: non-metabolic risk (non-MR) NAFLD, MAFLD but not NAFLD, and overlapping FLD. Incident CKD was defined as the occurrence of eGFR < 60 mL/min/1.73m2 or proteinuria (≥ trace) on two consecutive health examinations. RESULTS: 73,726 (27.4%) and 88,762 (33.0%) participants had NAFLD and MAFLD, respectively. During a median follow-up of 5.1 years, CKD occurred in 8,335 (6.2/1,000 person-years) participants. Compared to non-NAFLD participants, the adjusted hazard ratio (aHR) for incident CKD was 1.33 (95% CI, 1.27-1.39; P < 0.001) for participants with NAFLD. Compared to non-MAFLD participants, the aHR for participants with MAFLD was 1.39 (95% CI, 1.33-1.46; P < 0.001). When the analysis was confined to participants with FLD, compared to non-MR NAFLD participants, the aHRs for participants with MAFLD but not NAFLD, and those with overlapping FLD were 1.18 (95% CI, 1.01-1.39; P = 0.040) and 1.36 (95% CI, 1.19-1.54; P < 0.001), respectively. CONCLUSION: MAFLD identified a higher proportion of individuals at risk of developing CKD than NAFLD.

Technique for analyzing the transfer of colored cosmetics onto face masks.

BACKGROUND: With the rapid spread of COVID-19, the makeup trend in the cosmetics market is changing as mask-wearing has become a common practice. This study was conducted to establish an objective and reliable method for analyzing the transfer of colored cosmetics onto face masks. METHODS: A total of 24 women participated in this test. The participants were requested to wear Korean Filter 94 masks after having applied colored cosmetics on their faces and lips. VISIA-CR was used to photograph the face, and a camera was used to photograph the mask, which had smeared the cosmetics. Each image was analyzed using the Image-pro® 10 image analysis software. RESULTS: Immediately after applying the cosmetics, the intensity of the face decreased and the redness of the lips increased when compared with the results 30 minutes after washing the face. After wearing a mask, the intensity increased and the redness decreased when compared with immediately after applying the cosmetics. The area before and after the colored cosmetics smeared onto the mask was increased. CONCLUSION: It is expected that this study could be used as a reference for further experiments on analysis of methods for preventing mask stains.

Changes in skin wrinkles and pores due to long-term mask wear.

BACKGROUND: The spread of COVID-19 has made mask wear essential. Expecting that long-term mask wear would change the characteristics of skin, this study investigated changes in skin wrinkles and pores caused by long-term mask wear and whether or not use of moisturizers has an effect on any changes. MATERIALS AND METHODS: The study participants were 20 women who were instructed to wear a mask for at least 6 hours a day for 4 weeks. Measurements of skin wrinkles and pores were obtained before and after the 4 weeks of mask wear. The effects of application of a moisturizer were assessed by applying moisturizer within the mask-wearing area. They completed a questionnaire about skin changes at the end of the study period. RESULTS: After wearing the mask for 4 weeks, there was a significant increase in the skin wrinkles and pores; both variables decreased significantly in skin areas where a moisturizer had been applied. The results of the questionnaire-based survey indicated the study participants considered that long-term wearing of a mask had affected their skin. CONCLUSION: Wearing a mask for extended periods increases skin wrinkles and pores and using a moisturizer when wearing the mask helps to reduce this problem.

SD-OCT parameters and visual field defect in chiasmal compression and the diagnostic value of neural network model.

PURPOSE: To evaluate the peripapillary retinal nerve fiber layer (RNFL) and macular ganglion cell-inner plexiform layer (GCIPL) measurements using spectral domain optical coherence tomography (SD-OCT) in patients with chiasmal compression and analyze the diagnostic value of a neural network model. METHODS: Forty-seven patients with chiasmal compressive disorder were recruited and divided into two groups depending on the visual field defect (perimetric; group 1 and preperimetric; group 2). Fifty-seven normal subjects were also recruited (group 3). Peripapillary RNFL and macular GCIPL were analyzed in each group. A multilayer perceptron was trained using a training dataset and derived a neural network model. The diagnostic performances were compared using the area under the receiver operating curve (AUROC) between each parameters and neural network model. RESULTS: All macular GCIPL parameters, except inferotemporal GCIPL thickness, were thinner in group 1 than in group 2 and group 3, with barely any difference between group 2 and group 3 parameter values. The diagnostic power of the neural network model, minimum GCIPL, and inferonasal GCIPL were superior when compared with other parameters; the diagnostic values of these three parameters are not significantly different in discriminating the patients and normal control. However, the neural network exhibited the best diagnostic power in distinguishing group 2 and group 3. CONCLUSION: Macular GCIPL was reduced in chiasmal compression patients with visual field defect which was not evident in the preperimetric state. Neural network model showed superior diagnostic value in discriminating the preperimetric patients from normal control. The results suggest that neural networks may be helpful in the early diagnosis of chiasmal compression.

Low High-Sensitivity C-Reactive Protein Level in Korean Patients With Chronic Kidney Disease and Its Predictive Significance for Cardiovascular Events, Mortality, and Adverse Kidney Outcomes: Results From KNOW-CKD.

Background Inflammation levels are lower in East Asians than in Western people. We studied the association between high-sensitivity hs-CRP (C-reactive protein) and adverse outcomes in Korean patients with chronic kidney disease. Methods and Results We included 2018 participants from the KNOW-CKD (Korean Cohort Study for Outcome in Patients With Chronic Kidney Disease) between April 2011 and February 2016. The primary outcome was a composite of extended major cardiovascular events (eMACE) or all-cause mortality. The secondary end points were separate outcomes of eMACE, all-cause death, and adverse kidney outcome. We also evaluated predictive ability of hs-CRP for the primary outcome. The median hs-CRP level was 0.60 mg/L. During the mean follow-up of 3.9 years, there were 125 (6.2%) eMACEs and 80 (4.0%) deaths. In multivariable Cox analysis after adjustment of confounders, there was a graded association of hs-CRP with the primary outcome. The hazard ratios for hs-CRPs of 1.0 to 2.99 and ≥3.0 mg/L were 1.33 (95% CI, 0.87-2.03) and 2.08 (95% CI, 1.30-3.33) compared with the hs-CRP of <1.0 mg/L. In secondary outcomes, this association was consistent for eMACE and all-cause death; however, hs-CRP was not associated with adverse kidney outcomes. Finally, prediction models failed to show improvement of predictive performance of hs-CRP compared with conventional factors. Conclusions In Korean patients with chronic kidney disease, the hs-CRP level was low and significantly associated with higher risks of eMACEs and mortality. However, hs-CRP did not associate with adverse kidney outcome, and the predictive performance of hs-CRP was not strong. Registration URL: http://www.clinicaltrials.gov; Unique identifier: NCT01630486.

Evaluation of factors triggering sensitive scalp in Korean adult women.

BACKGROUND: The scalp care market is growing rapidly and research into the factors associated with sensitive scalp is performed in many countries. However, to the best of our knowledge, no previous study has examined the factors triggering sensitive scalp in Korean women. Thus, the aim of our study was to establish objective standards for sensitive scalp, investigate factors that trigger this condition, and determine the ratio of sensitive scalp in Korean women. METHODS: A total of 125 Korean adult women participated in the study. The participants answered the questionnaire, had their scalp temperature measured, and the sensitive scalp condition was evaluated and analyzed. RESULTS: Compared to the non-sensitive scalp (NS) group, the sensitive scalp (SS) group had a significantly higher average temperature and increased heat sensation, dandruff, erythema in the scalp, past history of atopy, history of hair loss, medical history of scalp disease, concern for scalp care, and interest in mild products and frequency of use. The majority of participants in the SS group had a dry scalp, and itching was common. CONCLUSION: This study may help us to understand the characteristics of the sensitive scalp in Korean females and determine factors associated with triggering a sensitive scalp.

Evaluation of human electroencephalogram change for sensory effects of fragrance.

BACKGROUND: The stabilizing effect of lavender and the arousal effect of peppermint essential oils are acknowledged and used widely in aromatherapy and the cosmetics industry. However, no evaluation method confirms the effects of essential oils through quantitative and objective electroencephalogram (EEG) results; instead, only a psychological and subjective method exists. Therefore, this study aims to create a new emotional cosmetic evaluation paradigm using EEG values. Moreover, it enables quantitative interpretation of the results in addition to the subjective survey outcomes. METHODS: For this study, 12 healthy female Korean participants were recruited and three fragrances were used. The EEG results were collected for 3 minutes (1 minute each before, during, and after inhalation of every fragrance). RESULTS: The quantitative EEG outcomes indicate changes in the participant's brainwaves before and after inhalation. Significant changes in the EEG were observed. Based on the results, the effects of fragrances were confirmed to be stabilizing for lavender, and arousing for peppermint and coffee aroma. Furthermore, the subjective questionnaire results indicate similar tendency as that of the quantitative EEG results. CONCLUSION: In addition to psychological and subjective assessments, our emotional evaluation method can verify the cosmetic fragrance effects through quantitative and objective results.

Cynandione A inhibits lipopolysaccharide-induced cell adhesion via suppression of the protein expression of VCAM­1 in human endothelial cells.

Cynandione A (CA) is one of the most active compounds in the roots of Cynanchum wilfordii, the extracts of which have been used extensively in East Asia to treat various diseases including anti­ischemic stroke. In the present study, the anti­adherent activity of CA in lipopolysaccharide (LPS)­stimulated human umbilical vascular endothelial cells (HUVECs) was investigated. CA markedly reduced the expression of vascular adhesion molecule­1 (VCAM­1) by LPS in HUVECs. The results also demonstrated that CA significantly reduced the expression of pro­inflammatory and chemoattractant cytokines, including interleukin (IL)­1ß, IL­6, IL­8, monocyte chemoattractant protein­1 and tumor necrosis factor­α, in LPS­activated human endothelial cells. CA inhibited the phosphorylation of mitogen­activated protein kinases, including the extracellular signal­regulated kinase 1/2 and p38 kinases. It was found that CA decreased the IKK/IκB­α phosphorylation of inhibitor of nuclear factor (NF)­κB kinase/inhibitor of NF­κB­α, suppressed translocation of the NF­κB p65 subunit into the nucleus and inhibited the transcriptional activity of NF­κB. CA also decreased human monocyte cell adhesion to endothelial cells in LPS­stimulated conditions. These results demonstrated that CA inhibited the protein expression of VCAM­1 and pro­inflammatory cytokines by suppressing the transcriptional activity of NF­κB. The results also suggested that CA may be important in the development of anti­inflammatory drugs by inhibiting the expression of cell adhesion molecules.

Cynandione A attenuates lipopolysaccharide-induced production of inflammatory mediators via MAPK inhibition and NF-κB inactivation in RAW264.7 macrophages and protects mice against endotoxin shock.

Cynanchum wilfordii has been traditionally used in eastern Asia for the treatment of various diseases such as gastrointestinal diseases and arteriosclerosis. Cynandione A (CA), an acetophenone, is one of major constituents from roots of C. wilfordii. In the present study, the anti-inflammatory activities of CA were investigated in lipopolysaccharide (LPS)-treated RAW264.7 macrophages and LPS-administered C57BL/6 N mice. CA significantly decreased LPS-induced production of nitric oxide and prostaglandin E2 in a dose-dependent manner, while CA up to 200 µM did not exhibit cytotoxic activity. Our data also showed that CA significantly attenuated expression of iNOS and COX-2 in LPS-stimulated macrophages. CA inhibited phosphorylation of IκB-α and MAP kinases such as ERK and p38. Furthermore, we demonstrated that CA inhibited translocation of NF-κB to the nucleus, transcription of the NF-κB minimal promoter and NF-κB DNA binding activity. Administration of CA significantly decreased the plasma levels of pro-inflammatory cytokines such as TNF-α, IL-6, and IL-1ß in LPS-injected mice and improved survival of septic mice with lethal endotoxemia. These results demonstrate that CA has effective inhibitory effects on production of inflammatory mediators via suppressing activation of NF-κB and MAPK signaling pathways, suggesting that CA may be used as a potential anti-inflammatory agent for the prevention and treatment of inflammatory diseases.

Jaceosidin, a natural flavone, promotes angiogenesis via activation of VEGFR2/FAK/PI3K/AKT/NF-κB signaling pathways in endothelial cells.

Angiogenesis, the growth of new blood vessels from pre-existing vasculature, plays an important role in physiological and pathological processes such as embryonic development wound healing and revascularization of tissues after exposure to ischemia. We investigated the effects of jaceosidin, a main constituent of medicinal herbs of the genus Artemisia, on angiogenesis and signaling pathways in endothelial cells. Jaceosidin stimulated proliferation, migration and tubulogenesis of ECs as well as ex vivo sprouting from aorta rings, which are phenomena typical of angiogenesis. Jaceosidin activated vascular endothelial growth factor receptor 2 (VEGFR2, FLk-1/KDR) and angiogenic signaling molecules such as focal adhesion kinase, phosphatidylinositol 3-kinase, and its downstream target, the serine-threonine kinase AKTWe also demonstrated that jaceosidin activated the NF-κB-driven expression of a luciferase reporter gene and NF-κB binding to DNA. Jaceosidin-induced proliferation and migration of human umbilical vascular endothelial cells were strongly inhibited by the phosphatidylinositol 3-kinase inhibitor LY294002 and NF-κB inhibitor BAY11-7082, indicating that the PI3K/AKT/NF-κB signaling pathway is involved in jaceosidin-induced angiogenesis. Our results suggest that jaceosidin stimulates angiogenesis by activating the VEGFR2/FAK/PI3K/AKT/NF-κB signaling pathway and that it may be useful in developing angiogenic agents to promote the growth of collateral blood vessels in ischemic tissues.

A novel synthetic compound 3-amino-3-(4-fluoro-phenyl)-1H-quinoline-2,4-dione (KR22332) exerts a radioprotective effect via the inhibition of mitochondrial dysfunction and generation of reactive oxygen species.

PURPOSE: Acute side effects of radiation such as oral mucositis are observed in most patients. Although several potential radioprotective agents have been proposed, no effective agent has yet been identified. In this study, we investigated the effectiveness of synthetic compound 3-amino-3-(4-fluoro-phenyl)-1H-quinoline-2,4-dione (KR22332) as a radioprotective agent. MATERIALS AND METHODS: Cell viability, apoptosis, the generation of reactive oxygen species (ROS), mitochondrial membrane potential changes, and changes in apoptosis-related signaling were examined in human keratinocyte (HaCaT). RESULTS: KR22332 inhibited irradiation-induced apoptosis and intracellular ROS generation, and it markedly attenuated the changes in mitochondrial membrane potential in primary human keratinocytes. Moreover, KR22332 significantly reduced the protein expression levels of ataxia telangiectasia mutated protein, p53, and tumor necrosis factor (TNF)-α compared to significant increases observed after radiation treatment. CONCLUSION: KR22332 significantly inhibited radiation-induced apoptosis in human keratinocytes in vitro, indicating that it might be a safe and effective treatment for the prevention of radiation-induced mucositis.

The stimulatory effects of Stewartia koreana extract on the proliferation and migration of fibroblasts and the wound healing activity of the extract in mice.

Stewartia koreana (S. koreana) has been used in the treatment of inflammatory diseases, such as acute gastroenteritis and aches, in Korean folk medicine and has been reported to have a number of biological activities, such as anti-inflammatory activity and the promotion of angiogenesis. In this study, we aimed to determine the effects of S. koreana extract (SKE) and its components on dermal fibroblast growth and migration, and to investigate the wound healing activity of the extract in mice. In vitro experiments revealed that the numbers of SKE-treated cells increased by approximately 2.5-­ and 3.7-fold with 50 and 100 µg/ml of SKE, respectively. 5-bromo-2'-deoxy-uridine (BrdU) incorporation was also increased in the SKE-treated cells by 2.3-fold. SKE promoted the migration of human skin fibroblasts and, among the isolated compounds, hyperin increased the proliferation and migration of the fibroblasts to almost the same degree as SKE. Western blot analysis demonstrated that SKE stimulated the MEK/ERK1/2 and PI3K/Akt signaling pathways. In in vivo experiments, the SKE-treated wound lesions of mice decreased by approximately 7% in diameter after 2 days of treatment with SKE compared with the wound lesions on the 1st day of the experiment. On the 9th day of treatment, the diameter of the lesions was further reduced by approximately 83% in the SKE-treated wound areas compared with the wound areas on the 1st day of treatment. Our results demonstrate that methanol extracts of S. koreana leaves promote the proliferation and migration of skin fibroblasts and possess effective wound healing activity through the activation of the MEK/ERK1/2 and PI3K/Akt signaling pathways. Hyperin was identified as an active compound responsible for the stimulation of fibroblast growth and migration.

Radioprotective effect of epicatechin in cultured human fibroblasts and zebrafish.

Radiation-induced normal cell damage limits the delivery of high-dose radiation to targeted cancer. This study investigated the effect of epicatechin (EC), a minor component of green tea extracts, on radiation-induced cellular damage in vitro in primary cultured human fibroblasts and in vivo in a zebrafish model. Cell viability, proliferation and wound-healing efficacy, mitochondrial membrane potential, and reactive oxygen species (ROS) generation as well as changes in the signaling pathway related to apoptosis were investigated in fibroblasts. The therapeutic effects of EC were explored in a zebrafish model. EC increased clonogenic survival and restored the migration ability of the fibroblasts after irradiation. EC inhibited radiation-induced ROS generation, mitochondrial dysfunction and cell death. EC significantly reduced the expression of p-JNK, p-38, and cleaved caspase-3 compared with their significant increase after radiation treatment. EC attenuated the radiation-induced embryotoxicity in a zebrafish model. These results suggest that EC represents an effective means of reducing cellular damage and facilitating wound healing after radiation exposure.

Protective effects of Korean red ginseng against radiation-induced apoptosis in human HaCaT keratinocytes.

Radiation-induced oral mucositis is a dose-limiting toxic side effect for patients with head and neck cancer. Numerous attempts at improving radiation-induced oral mucositis have not produced a qualified treatment. Ginseng polysaccharide has multiple immunoprotective effects. Our aim was to investigate the effectiveness of Korean red ginseng (KRG) on radiation-induced damage in the human keratinocyte cell line HaCaT and in an in vivo zebrafish model. Radiation inhibited HaCaT cell proliferation and migration in a cell viability assay and wound healing assay, respectively. KRG protected against these effects. KRG attenuated the radiation-induced embryotoxicity in the zebrafish model. Irradiation of HaCaT cells caused apoptosis and changes in mitochondrial membrane potential (MMP). KRG inhibited the radiation-induced apoptosis and intracellular generation of reactive oxygen species (ROS), and stabilized the radiation-induced loss of MMP. Western blots revealed KRG-mediated reduced expression of ataxia telangiectasia mutated protein (ATM), p53, c-Jun N-terminal kinase (JNK), p38 and cleaved caspase-3, compared with their significant increase after radiation treatment. The collective results suggest that KRG protects HaCaT cells by blocking ROS generation, inhibiting changes in MMP, and inhibiting the caspase, ATM, p38 and JNK pathways.

Effect of epicatechin against radiation-induced oral mucositis: in vitro and in vivo study.

PURPOSE: Radiation-induced oral mucositis limits the delivery of high-dose radiation to head and neck cancer. This study investigated the effectiveness of epicatechin (EC), a component of green tea extracts, on radiation-induced oral mucositis in vitro and in vivo. EXPERIMENTAL DESIGN: The effect of EC on radiation-induced cytotoxicity was analyzed in the human keratinocyte line HaCaT. Radiation-induced apoptosis, change in mitochondrial membrane potential (MMP), reactive oxygen species (ROS) generation and changes in the signaling pathway were investigated. In vivo therapeutic effects of EC for oral mucositis were explored in a rat model. Rats were monitored by daily inspections of the oral cavity, amount of oral intake, weight change and survival rate. For histopathologic evaluation, hematoxylin-eosin staining and TUNEL staining were performed. RESULTS: EC significantly inhibited radiation-induced apoptosis, change of MMP, and intracellular ROS generation in HaCaT cells. EC treatment markedly attenuated the expression of p-JNK, p-38, and cleaved caspase-3 after irradiation in the HaCaT cells. Rats with radiation-induced oral mucositis showed decreased oral intake, weight and survival rate, but oral administration of EC significantly restored all three parameters. Histopathologic changes were significantly decreased in the EC-treated irradiated rats. TUNEL staining of rat oral mucosa revealed that EC treatment significantly decreased radiation-induced apoptotic cells. CONCLUSIONS: This study suggests that EC significantly inhibited radiation-induced apoptosis in keratinocytes and rat oral mucosa and may be a safe and effective candidate treatment for the prevention of radiation-induced mucositis.

Enhancement of CCL15 expression and monocyte adhesion to endothelial cells (ECs) after hypoxia/reoxygenation and induction of ICAM-1 expression by CCL15 via the JAK2/STAT3 pathway in ECs.

CCL15, a member of the CC chemokine family, is a potent chemoattractant for leukocytes and endothelial cells (ECs). Given that chemokines play key roles in vascular inflammation, we investigated the effects of hypoxia/reoxygenation (H/R) on expression of human CCL15 and a role of CCL15 in upregulating ICAM-1 in ECs. We found that exposure of ECs to H/R increased expression of CCL15 and ICAM-1, which resulted in an increase in monocyte adhesivity to the ECs. Further studies revealed that knockdown of CCL15 or CCR1 attenuated expression of ICAM-1 in ECs after H/R, suggesting that expression of ICAM-1 is upregulated by CCL15. Stimulation of ECs with CCL15 significantly increased expression of ICAM-1 predominantly via the CCR1 receptor. We observed that phosphorylation of JAK2 and STAT3 was stimulated by CCL15 treatment of ECs. Results from reporter and chromatin immunoprecipitation assays revealed that CCL15 activates transcription from the IFN-γ activation site promoter and stimulates binding of STAT3 to the ICAM-1 promoter. Our data also showed that CCL15 increased cell adhesion of human monocytes to ECs under static and shear-stress conditions. Pretreatment of these cells with inhibitors for JAK, PI3K, and AKT prevented the CCL15-induced expression of ICAM-1 and monocyte adhesion to ECs, suggesting the involvement of those signaling molecules in ICAM-1 gene activation by CCL15. The results suggest that CCR1 and its ligands may be a potential target for treating inflammatory diseases involving upregulation of cell adhesion molecules.